RNA interference (RNAi) is a technique in which exogenous, double-stranded RNAs (dsRNAs) are introduced into a cell to specifically destroy a particular mRNA or block its expression, thereby diminishing or abolishing gene expression. Specific types of RNAs, such as small interfering RNAs (siRNAs) and micro interfering RNAs (miRNAs) have been shown to inhibit expression of a number of specific genes effectively and the technique has proven effective in various cell cultures, including mammalian cell cultures. Because small interfering RNA molecules are directed to a specific target and thereby silence a specific gene, they have been suggested to be useful in treatment of diseases as well as for screening new pharmaceuticals and disease mechanisms for pharmaceutical target determination. However, delivery of RNA interfering agents, including siRNAs and miRNAs, into cells has proven to be challenging.
Various methods to deliver RNA interference molecules into cells are known, and include chemical transfection using lipid-based, amine-based and polymer-based techniques, and combinations thereof. Unfortunately, efficient transfer of RNA interfering agents, including siRNAs into primary cells by chemical transfection seems to be restricted to a few cell types. Other ways to deliver siRNAs include expressing short hairpin RNA molecules from vectors include lentiviral constructs, and introducing siRNA molecules into cells using electroporation. However, these methods are also have shortcomings. Viral delivery has issues related to permanent integration and electroporation is a harsh treatment that cannot generally be used to deliver siRNAs into cells in vivo. Further, these RNA interference delivery methods target all cells non-specifically.
Therefore, it would be useful to develop RNAi delivery methods that target specific cells, thereby minimizing or avoiding potential side effects caused by delivery of RNA interference into non-target cells.